“You only see what you look for…and only look for what you know.” An axiom from medical school, often attributed to William Osler, though not confirmed. Nevertheless, an important aphorism in how we understand and put together the collection of symptoms presenting in clinic, particularly in the case of pyroluria.

I hadn’t heard of pyrroles until well past my formal education, when I started to unearth the orthomolecular medicine archives and explore that body of literature buried in the annals of nutritional interventions (the intervention likely the real reason why it isn’t so readily recognized in the mainstream medical community).

So what is pyroluria?

Pyrolouria is a genetic blood disorder having to do with the synthesis of red blood cells. During the production of hemoglobin, hydroxyhemoppyrrolin-2-one (HPL) is formed as a byproduct. In most people, this “harmless” byproduct is easily excreted through the urine. However, in some, the levels of HPL accumulate too quickly to be excreted efficiently. Pyrroles have a very high affinity for zinc and B6 (and also block the receptor sites for these two nutrients); as the excess pyrroles are excreted, they take with them these two vital nutrients, leading to zinc and B6 deficiency states. Zinc has many functions, including in the immune system, gut integrity, and neurotransmitter synthesis; among other things, B6 is essential for the synthesis of serotonin, dopamine and GABA. So as these nutrients dwindle, emotional and physical repercussion potentially crescendo.

The true etiology is unknown, but pyroluria appears to be a genetic condition as it does tend to run in families. However, it might also be thought of as more of an epigenetic phenomenon, as there is some evidence that it gets “activated” with trauma or infection or another environmental insult early in life. More on epigenetics will be written in a future post, but the gist is that epigenetics is the science of gene regulation- how our inherited genes get turned on and off.

It’s estimated that approximately 11% of people in the general population have pyroluria, often being referred to in functional medicine as the most common unknown disorder. When you look at the psychiatric community, the incidence skyrockets (shown below in percentage with elevated pyrroles):*

71% in Down’s syndrome,

59-80% in acute schizophrenia

40-50% in chronic schizophrenia

47-50% in manic depression/Bipolar

12-46% in major depression

46-48% in autism

40-47% in ADHD/ADD

40-47% in learning disabilities

20-84% in alcoholism

71% in acute onset adult ciminal behaviors

33% in young violent offenders

The common symptoms are (incomplete list):

very poor stress tolerance

white spots on finger nails (from zinc deficiency)

sensitivity to bright lights

sensitivity to loud noises

skin sensitivities (tags on shirts, textures/materials)

abnormal fat distribution (large middle, skinny arms/legs)

irritable bowel syndrome

abdominal/splenic area pain

delayed onset of puberty (late bloomer, growth after 16years of age)

irregular periods/menstrual cycles

pale skin

tendency to burn (instead of tan)

overcrowded teeth/poor tooth enamel

joint pains (cold hands/feet, creaky knees)

anxiety

social isolation/withdrawal

mood swings/irritability/explosive anger/tantrums

depression

disorganization

history of reading disorder

focus/concentration difficulties

motion sickness

auditory processing disorders

poor short term-memory/poor dream recall

insomnia

fatigue

hyperactivity/ADHD symptoms

craving for sugar/carbs

carving for spicy/salty foods

poor morning appetite/morning nausea

frequent infections

impotence

glucose intolerance

sweet or fruity body odor or breath

paranoia/hallucinations

seizures

very dry skin

psoriasis

tendency to stay up late at night/night owl.

And of course, with deficient zinc, free copper levels might escalate with the ensuing problems of high anxiety, poor concentration, tinnitus, explosive anger, and estrogen intolerance. As you can see from the list, these symptoms are very common to many disorders, so this condition is frequently diagnosed as ADHD, Bipolar Disorder, learning disorders, intermittent explosive disorder, etc, with the ensuing treatments for those disorders being put in place without replacing the essential micronutrients.

Diagnosis is typically clinical with substantiation through urinary kryptopyrrole testing. It will be important to measure zinc, copper and ceruloplasmin as well to understand the degree of zinc deficiency and free copper excess so that the appropriate interventions can be made. Treatment is largely based on replacing the deficient nutrients of B6 and Zinc, but is also dependent on multiple other factors that generally require a health care professional to supervise.

Until we know what to look for, pyroluria will remain a largely unrecognized, and therefore untreated illness masquerading as (and exacerbating) the sundry other psychiatric ailments.

We really have to reconsider what MTHFR testing means, which also means re-evaluating my earlier post on MTHFR and its treatment. Just to recap, MTHFR is an enzyme in the biochemical pathway to methylate folate (i.e. add a methyl-group- a carbon and 3 hydrogens- to folic acid); methylfolate then donates its methyl group to vitamin B12 (cobalamin). The sole purpose of this enzyme is to add this methyl-group. There are numerous polymorphisms in the MTHFR enzyme, the two most significant being the C677T and the A1298T. However, there are A LOT of enzymes in the whole methylation cascade, all with potential SNPs (single nucleotide polymorphisms). In our/my nascent understanding of MTHFR mutations, all mutations were assumed to have a deleterious effect on the brain (and body) and were treated with methylfolate as a means to bypass this errant enzyme, with the assumption the under-methylation was the main problem. However, MTHFR mutations do not necessarily mean methylation problems, as it could certainly be offset by another polymorphism elsewhere in the pathway. Interestingly, folate is assumed to be a good methylator. The reality, though, is that for every methyl group donated by folate (in the cytoplasm), ten methyl groups are removed from the nucleus, where the effect on the DNA is really felt (thanks to Dr. Albert Mensah for his great insights and help in understanding this!). Folate essentially exacerbates undermethylation problems and is likely why some people actually get worse when methylfolate (or any folate, including dietary folate like in kale) is added. It is certainly more complex than this, but the gist of what I’m really saying is that MTHFR status might be important, like in the potential contribution to elevated homocysteine in heart disease, but the the bigger picture has to do with overall methylation status, for which MTHFR mutations are not a direct indicator.

A far better test to assess overall methylation status would be to look at histamine levels in the body, as histamine is cleared from the body through methylation. High histamine levels roughly equate with under-methylation; low histamine, with over-methylation. The test for whole blood histamine is fragile and requires special handling in the lab; fortunately, the Chicago based Direct Health Care Access lab has mastered this process and can educate/coordinate with other labs around the county on this process (http://pyroluriatesting.com).

Methylation status is important to know as it dramatically effects how we think and feel, what are risks are (i.e. depression, anxiety, OCD, anxiety, etc), how we respond to certain interventions, and, most importantly, how we can potentially alter the course of our genetic inheritance to live longer, healthier, happier lives. After all, it is about wellness in the end.

For more information on methylation (which will also be posted later), I highly recommend the pioneering work of Dr. William Walsh, and in particular his book, Nutrient Power. He works closely with Dr. Albert Mensah and Dr. Judith Bowman of Mensah Medical (www.mensahmedical.com). Their website is a tremendous wealth of information on biochemical interventions and understanding brain chemistry.

One of the greatest tools that we have to address anxiety and stress is the breath.

Given the relationship between stress and almost all illness, the importance of this simple remedy cannot be overemphasized. Dr. Andrew Weil, medical pioneer and director of the University of Arizona’s Integrative Medicine Program, has remarked that if he were allowed only one tool to treat illness, he would use breath work. Breathing is the nexus between the conscious and the unconscious mind, the connection between the mind and the body. It is no coincidence that in many cultures the words for breathe and spirit are the same, like the Sanskrit word prana, and why most spiritual practices begin with a focus on breathing. Continue reading… »

As you simplify your life, the laws of the universe will be simpler; solitude will not be solitude, poverty will not be poverty, nor weakness weakness. ~ Henry David Thoreau

Beware the barrenness of a busy life. ~Socrates

I recently attended a lecture by Kim John Payne, M.Ed promoting his philosophy (and book), Simplicity Parenting. The gist of his approach is appropriately simple: simplify our children’s lives so that their development can naturally unfold. Continue reading… »

By far and away the most common concern that I see in my pediatric clinic pertains to the question of ADHD. It usually stems from a concern about school performance, but the real underlying query has to do with whether the problem is or is not ADHD. Unfortunately, psychiatrists in general have been pigeonholed into a predicament whereby medications are often the first line or only treatment. In some other countries, medications lie on the opposite end of the spectrum and are treated as a last resort, only after various therapeutic interventions have been undertaken. The right path is likely somewhere in the middle between therapy and medications, as medications (whether over-the-counter or prescribed) do offer quick relief in many circumstances where therapy cannot gain a foothold for the severity of the symptoms, and medications do work to alleviate symptoms in ADHD, sometimes immediately so. ADHD is indeed the bread and butter of most general child & adolescent psychiatric practices. It is the most studied of all of the childhood psychiatric problems, with well over 200 clinical trials investigating it and it’s treatment. Though some might argue that ADHD is an illness manufactured by the pharmaceutical industry in order to push stimulant sales, there is no doubt in my mind that ADHD exists in some form or another. The problem really, though, is “What is it?“. Continue reading… »

MTHFR stands for the mehylenetetrahydrofolatereductase gene. It is located on chromosome 1 and is responsible for making the MTHFR enzyme. This enzyme is essential for processing amino acids. Specifically, it converts folate (vitamin B9) into a usable form (converting 5,10-methylentetrahydrofolate to 5-methyltetrahydrofolate) which is needed in the reaction to convert the amino acid homocysteine to methionine. It is also needed to make neurotransmitters (dopamine, norepeniphrine, serotonin) and glutathione (which is your body’s main detoxifier). Excessive homocysteine (hyperhomocystenima) can lead to cardiovascular disease and thrombosis (to name just a few problems) and is often associated with infertility. Continue reading… »

According to an October 2010 study*, the top sources for calories for 2-18 year-olds in the US were grain desserts (cookies, cakes, granola bars), pizza, and soda, with nearly 40% of the consumed calories coming from empty-calorie foods. The fact that no one was surprised by these results is testament to our apathy and/or our own nutritional deprivation. Also unfortunately not shocking in the general public is that we are seeing illnesses escalating in this pediatric population that were formerly reserved for the middle & late age range, like type II diabetes. Just look around and you’ll see evidence of our society’s declining health. And the main source of our woes is not bad genes (though, rest assured it is a nature and nurture situation), but our environment, and more specifically, our nutritional environment, our mealiue, as it were. Continue reading… »

DMAE stands for dimethylaminoethanol. It is related to choline, which is part in the B- vitamin complex. Choline has three main roles: cell structural integrity and signaling, acetylcholine synthesis and cholinergic neurotransmission, and as a major source for methyl-groups through it’s metabolite betaine (trimethylglycine), which subsequently participates in S-adenyslmethinoine (SAMe) synthesis (more on the methylation process in a later blog…). Continue reading… »

“This is the most alarming book I’ve read in years,” wrote Carl Elliot, MD, PhD (professor, Center for Bioethics, University of Minnesota), reviewing Anatomy of an Epidemic by Robert Whitaker. I agree wholeheartedly. Not disturbing like clowns, but more like the truth-behind-the-collapse-of-the-economy kind of disturbing. This is one of those books that gets under your skin and profoundly changes the way that you look at the world, or at least my world, the world of modern psychiatry. You cannot come away from this book unchanged. Anatomy of an Epidemic is an essential read for anyone in mental health- on both ends of the continuum from prescribers to consumers. Actually, given the vast reach and breadth of psychopharmocology’s influence, I would venture to say that this book is essential reading for everyone, since everyone is bound to know someone under the influence, as it were, and the deceptions revealed in this book are likely not limited to the psycho/pharmaceutical industry. Continue reading… »

There are 4 main food sensitivities that seem to affect kids the most: milk, wheat, soy, & eggs.

I’ll spend a little time later on the wheat/gluten concerns, but for now I want to talk just a little about milk and dairy sensitivities, given that milk and cookies have pretty much formed the staple of the holiday diet.

Generally speaking, nutritional related problems fall into 2 broad categories: deficiencies and irritants. As described in prior posts, we as a whole tend to be nutritionally deficient when it comes down to optimum health. That slow & steady depletion, much like a slow leak, will eventually lead to health problems. Except in extreme cases, gross, single nutrient deficiencies are relatively rare (though Vitamin D – which is technically a hormone- seems to be low in almost everyone that I test- but more on that in a later post). Continue reading… »

SEARCH

Subscribe via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

ABOUT THIS SITE

I am a practicing child/adolescent/adult psychiatrist in Tennessee. This site is about exploring integrative mental health care. It is not, as the title might imply, a polemic against medication use, as there is absolutely a role for psychopharmacology. Rather, it is about alternative ways to approach illness that might be safer, cheaper, and potentially healthier first steps. I intend to share information that I find interesting, essential, and hopeful as a psychiatrist, parent, and citizen-consumer. This information is for educational purposes only, and should not be used as personal medical advice.